Paralysis monitoring system

ABSTRACT

A paralysis monitoring system can be utilized during various medical procedures. Generally, the system is used during procedures involving anesthesia, when general paralysis is necessary, e.g., during surgery that requires cutting through or mobilizing muscle tissue. The paralysis monitoring system stimulates a nerve with low voltage signals and can provide for continuous monitoring and recording of the evoked muscle activity throughout and after a procedure. By monitoring a quantitative response of the muscle activity to nerve stimulation, an anesthesiologist may adjust subsequent doses of a paralytic agent to achieve a desired level of paralysis.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/469,797, to Bray, filed Mar. 10, 2017, and titled “ParalysisMonitoring System,” the entirety of which is herein incorporated byreference.

BACKGROUND

Paralysis monitoring systems can be utilized during various medicalprocedures. Generally, these systems are used during proceduresinvolving anesthesia, when general paralysis is necessary, e.g., duringsurgery that requires access through muscle tissue. During suchprocedures, healthcare professionals (such as physicians,anesthesiologists, doctors, surgeons, technicians, and otherhealth-related personnel) generally utilize different techniques thatcan indicate to some extent the level of paralysis of a patient. In somecases, physicians have typically utilized a stimulating probe withvisual documentation of muscle contraction, which is conventionallyreferred to as a “train-of-four.” This type of conventionalneuromuscular monitoring is used during the application of generalanesthesia with paralysis to determine approximately how well apatient's muscles are able to function. The conventional train-of-fourmonitoring technique is applied intermittently. The conventionaltechnique uses four stimulating electrical impulses of approximately 20mV that are placed over the nerve in a superficial area, such as theface, elbow, ulnar nerve or peroneal nerve in the leg. During theconventional train-of-four monitoring, the physician looks for grossmotor motions of the patient to ascertain that the level of paralysisadministered to the patient with a long-acting depolarizing agent isadequate, indicating a loss of muscle activity, as well as for signsthat activity has begun to return so that anesthesia may be terminated.When a patient is under paralysis there is a loss of the train-of-fourresponses.

The conventional train-of-four monitoring technique involves stimulationof the nerve and contemporaneous visual observation and documentation ofspasms or reactions of the muscle. As paralysis or paralytic agents—suchas curare derivative agents or nondepolarizing agents—are administered,a neuromuscular blockade of a patient's muscle activity can occur. Thetrain-of-four technique is typically used after the administration ofthe paralysis agent to document that the ability to move has been lostand the patient is now “paralyzed”. The technique is also used at theend of a procedure to demonstrate a return of the train-of-fourresponses, such that a patient may be extubated from anesthesia.

As will be described below, there are several drawbacks to the use ofthe conventional ‘train-of-four’ technique. It is understood that thetrain-of-four tests cannot be repeated more than a few times because ofthe high stimulus used, which can create a burning effect of the nerve,numbness, tingling and painful dysesthesias of the nerve. Thus, thisconventional technique cannot be used as a continuous monitoring device.Further, prior to a surgical procedure, patients are typically preloadedwith a heavy dose of a paralytic agent, which is allowed to wear offover time. However, the dosage and administration of the drug may beassociated with highly variable responses as its metabolism varies fromone patient to another patient. Thus, train-of-four neuromuscularmonitoring can be quite inaccurate in ascertaining whether completeparalysis has occurred or reversed. In some cases, during a procedure,there will be a loss of the train-of-four impulse recordings althoughthe patient has not yet reached a state of complete paralysis. Inaddition, because the length of time and metabolism of the drug is quitevariable, there can be situations where inadequate paralysis is obtainedduring the procedure. There can also be difficulty maintaining muscleretraction, and there may be other significant problems, such asincreased bleeding and loss of exposure, when muscle retraction returns.

Furthermore, if paralysis remains present when the procedure iscompleted and the anesthesia is allowed to wear off or lighten overtime, there is the risk that a patient may awaken or regainconsciousness while still in a state of paralysis. In other words, thepatient can go through a period where he or she is too weak to breathe,and/or unable to move. This can be a highly distressful or panic-evokingexperience for the patient. A reversal agent for the paralysis drug canbe given to the patient, but these drugs have other shortcomings. Forexample, reversal agents are typically short-acting, and generallyadministered at the end of a procedure. The patient would begin toexperience a decrease in paralysis and wake up and move, but withinapproximately 20-30 minutes the effects of the reversal agent can wearoff. If the paralysis agent has not been fully metabolized, the patientwill automatically re-paralyze at this point, which can lead torespiratory dysfunction or even death. This has been documented inpost-anesthesia cases if the patient is unobserved during this period.Additional doses of a reversal agent cannot be given as they have aparadoxical effect of recreating paralysis because the metabolism timeand dosing are very variable. Thus, it is very difficult for ananesthesiologist to determine the proper dose for each individual.Furthermore, there is reluctance to increase the dosage of the paralysisagent during the middle or end of the procedure case for fear that itwill not wear off and there will be difficulties awakening the patientunder paralysis.

As described, prior or conventional paralysis monitoring techniques usedin this area of medicine can only be used very intermittently, and areinaccurate in determining the level of paralysis. Such systems do notallow continuous monitoring that is critical to determining the level ofparalysis under anesthesia. In addition, these systems cannot be used inconscious patients due to the level of pain that can be caused.

SUMMARY OF THE INVENTION

In one aspect, a paralysis monitoring system includes a nervestimulation device configured to deliver a series of low voltageelectrical impulses to a nerve to produce only sub-visible muscleresponses, and a recording device configured to record electricalactivity associated with an evoked muscle response caused by the seriesof low voltage electrical impulses.

In another aspect, a paralysis monitoring system includes a nervestimulation device configured to deliver a series of low voltageelectrical impulses to a nerve, a first recording device configured torecord electrical activity associated with an evoked muscle response tothe nerve stimulation device, and a second recording device configuredto record electrical activity associated with the series of low voltageelectrical impulses to the nerve. The first recording device isconfigured to be placed over a target muscle group associated with thenerve and the second recording device is configured to be disposed awayfrom the target muscle group.

In another aspect, a method of administering a paralysis drug includesattaching a stimulation device to a patient's anatomy, attaching arecording device to the patient's anatomy and administering a first doseof a paralysis agent to the patient. Following this, the method includestransmitting low voltage electrical impulses from the stimulation deviceto the patient, receiving a response signal corresponding to muscleactivity of the patient in the recording device and using informationrelated to the response signal to determine an amount of the paralysisagent to administer as a second dose. Then the second dose of theparalysis agent may be delivered to the patient.

Other systems, methods, features, and advantages of the embodiments willbe, or will become, apparent to one of ordinary skill in the art uponexamination of the following figures and detailed description. It isintended that all such additional systems, methods, features, andadvantages be included within this description and this summary, bewithin the scope of the embodiments, and be protected by the followingclaims.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodiments can be better understood with reference to the followingdrawings and description. The components in the figures are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the embodiments. Moreover, in the figures, likereference numerals designate corresponding parts throughout thedifferent views.

FIG. 1 is a schematic view of two embodiments of components of aparalysis monitoring system constructed according to the principles ofthe invention;

FIG. 2 is flow chart illustrating an exemplary overall method ofoperation of the exemplary paralysis monitoring systems of FIG. 1;

FIG. 3 is a flow chart illustrating in more detail the initializationand preparation for continuous monitoring step of the method ofoperation of the paralysis monitoring system shown in FIG. 2;

FIG. 4 is a flow chart illustrating in more detail the steps ofcontinuously monitoring the onset of paralysis, paralysis after onsetand recovery steps of the method of operation of the paralysismonitoring system shown in FIG. 2;

FIG. 5 illustrates an exemplary spike discharge recording according theprinciples of the invention prior to administration of a paralysisagent;

FIG. 6 illustrates an exemplary spike discharge recording following theadministration of a paralysis agent;

FIG. 7 illustrates an exemplary spike discharge recording as theparalysis agent wears off;

FIG. 8 is a schematic view of placement of surface electrodes over thefacial nerve for stimulating a nerve according to the principles of theembodiments;

FIG. 9 is a schematic view depicting a type of stimulus generator thatmay be used to generate millivolt signals to be applied to a nerveaccording to the principles of the embodiments;

FIG. 10 is a schematic view of a type of monopolar point impulsegenerator that may be used to stimulate a nerve according to theprinciples of the embodiments;

FIG. 11 is a schematic view of another embodiment of a paralysismonitoring system applied over a limb;

FIG. 12 is a schematic view of a process for checking the functionalityof a paralysis monitoring system, according to an embodiment; and

FIG. 13 is a schematic view of several different electrical signals,according to an embodiment.

DETAILED DESCRIPTION

There is a need for a monitoring system that can reliably provideinformation pertaining to the neuromuscular condition of the patientbefore, during, and after a procedure. Current techniques do not permitmedical professionals to accurately ascertain whether a patient remainsparalyzed throughout the entirety of a procedure. During a surgicalprocedure—in particular during major procedures which can run severalhours—the safety of the patient becomes an increasingly difficultchallenge. The determination of the point at which it is safe toextubate the patient and/or the risk of employing too much paralysisagent are only some issues that can cause problems in recovery, leadingto situations where a patient is too weak to breathe. A monitoringsystem that overcomes these problems would provide healthcareprofessionals with a formidable lifesaving alternative.

The embodiments may avoid one or more of the drawbacks with theconventional train-of-four monitoring approach and may meet one or moreof the foregoing needs by providing a paralysis monitoring system thatallows for continuous monitoring of (a) the depth of paralysis present,(b) the level of reversibility of the patient, and/or (c) a safetymargin for extubation.

In addition, the exemplary embodiments of the invention includeprovisions for stimulation of nerves and uses 1/10 to 1/100 of thecurrent compared to the conventional train-of-four method, and mayrecord an evoked response from a muscle in the correspondingdistribution of the stimulated nerve. The nerve can be stimulatedtranscutaneously in some embodiments, the evoked muscle response can berecorded via either a small pin or a surface patch (Electromyogram,referred to as EMG), or a classic pin that is in contact with thedistributed muscles from the stimulated nerve or the muscle/nerveinterface. In contrast to the conventional train-of-four method, whichcan only be applied 3-4 times and relies upon an observed response,embodiments of the invention allow for repeated stimulations, due to theadministration of a current that ranges from 1/10- 1/100 relative to thecurrent used by the conventional train-of-four method. As an example,where the conventional train-of-four monitoring might administer astimulating current of 20-40 mA to a patient, embodiments of theinvention might only apply a current in a range between 0.2 mA-4 mA. Itshould be understood that these numbers are provided for comparisonpurposes only, and in other cases, the amount of current that isadministered using the inventive concepts could vary. It may beappreciated that the embodiments may use low voltages along with lowcurrents and in some cases the voltages could be substantially lowerthan the voltages applied during conventional train-of-four techniques.

In addition, in some embodiments muscle activity can be filtered outfrom the recording as noise while the evoked muscle response isrecorded. Thus, rather than rely upon visual observations of a muscleresponse, embodiments of the invention may record a graded returnresponse of evoked muscle activity. Furthermore, embodiments employingthe inventive concepts may provide a continuous monitoring technique inthe postoperative period.

Some of the advantages of the invention include a dramatic decrease inthe risks associated with paralysis during procedures requiringanesthesia, simplification of the processes of monitoring paralysisand/or administrating paralysis agents in precise, measured amountstailored to the individual patient's need. In addition, embodiments ofthe invention avoid reliance on conventional, crude visual observationsof muscle responses, and automatically accounts for the variability ofpatient physical characteristics such as skin thickness, temperature ofthe patient's extremities, etc., with a reliable neuromuscularrecording.

As shown in FIG. 1, in different embodiments, a paralysis monitoringsystem (“monitoring system”) 100 can be utilized during various medicalprocedures involving anesthesia when general paralysis is administered.Monitoring system 100 is capable of continuously monitoring the depth ofparalysis of a patient before, during and after the procedure requiringparalysis. Moreover, information obtained from monitoring system 100 maybe used when determining the quantity of a paralytic agent to beadministered at different points during a procedure.

Monitoring system 100 can include different components. FIG. 1 depictstwo different embodiments of monitoring system 100, denoted as a firstsystem 102 and a second system 104. In both first system 102 and secondsystem 104, the monitoring system includes a stimulation electrodedevice 110 and a recording device 120. The stimulation electrode devicemay be in the form of a pair of surface electrodes 800, as shown in FIG.8, or a bipolar stimulating probe, or another suitable stimulatingdevice. The recording device may be in the form of a recording surfaceelectrode or a pin recorder as shown in FIG. 1. First system 102 andsecond system 104 are shown together for illustrative purposes and itshould be understood that monitoring system 100 can comprise only onestimulation electrode device and one recording device in someembodiments. Furthermore, the type of stimulation electrode deviceand/or recording device utilized in monitoring system 100 can vary indifferent embodiments, as will be discussed below.

In different embodiments, stimulation electrode device 110 can comprisea transcutaneous skin stimulus with variable probe with electrodes orany other device capable of safely delivering milliamp pulses to humansat varying intensities. In some embodiments, monitoring system 100 is aconstant monitoring device that provides a single impulse to the nervesof a patient. The single impulse is read as a percentage of the baselinemonitoring (further detail regarding the baseline recording will bediscussed below).

A stimulation device is configured to deliver a low voltage (and lowcurrent) electrical signal to a region of tissue adjacent a nerve. Itmay be appreciated that different levels of voltage can have differenteffects on a target muscle (that is, the muscle associated with thetargeted nerve). For systems relying on a visual (or motion based)muscle response, the level of voltage generated by a stimulatingapparatus must be sufficient to contract the muscle to the point where amuscle twitch, or visual muscle contraction is observable. It may beappreciated, however, that lower voltages could be applied to evoke aresponse in a target muscle that is not directly observable with the eyeor other motion sensitive devices (e.g., accelerometers). For example,sufficiently low voltages might generate a “sub-visible response.” Asub-visible response may include a sub-visible contraction or asub-visible twitch that cannot be detected by a visual observation ofthe patient anatomy. During a sub-visible response, muscle fibers maycontract but the contraction may be insufficient (or the number offibers firing simultaneously is too few) to cause any substantialmovement that could be visually detected. However, though the muscle maynot move/twitch, electrical signals generated by the muscle in responseto the stimulation voltage may still be detectable by a recording devicecapable of sensing electrical signals (e.g., surface electrodes orsubcutaneous probes). By using recording devices that detect electricalsignals directly from the muscle, the embodiments provide a system thatcan make use of very low voltages compared to systems that rely onvisual or motion-based detection. Therefore, the embodiments may includesystems and methods for generating a voltage that is insufficient tocause a visible muscle response (e.g., visible contraction or twitch)and also of providing recording devices capable of detecting sub-visiblemuscle responses. Put another way, the embodiments use a stimulationdevice to generate low voltage signals that produce only sub-visibleresponses in a muscle and use a recording device capable of detectingthe sub-visible responses.

In different embodiments, the range of voltages generated by astimulation device during monitoring could vary. In some embodiments,the voltage could have any value approximately in a range between 0.1and 4 millivolts. In some embodiments, the range of voltages appliedcould vary according to factors including the size and weight of thepatient. For example, in some embodiments, the range of voltages appliedmay be approximately between 0.5 and 1.5 millivolts for patients havinga body mass index in a first range and the range of voltages applied maybe approximately between 1.5 and 4 millivolts for patients having a bodymass index in a second range that is higher than the first range. It maybe appreciated that body mass index is only one example of a parameterthat may be used to help determine an appropriate range of low voltagesignals to be applied by a stimulation device.

Because the monitoring system is configured to detect sub-visible muscleresponses, it may be more sensitive to subtle changes in muscle responsethan systems that rely on visually observable, or motion based,responses. This allows the muscle responses to be more readilyquantified so that the level of paralysis can be precisely determined.Moreover, the precision obtained using the exemplary system can begreater than the precision obtained using more conventional techniques(e.g., train-of-four) that are insensitive to any changes in muscleresponse that might occur at the sub-visible level.

In some embodiments, recording device 120 may comprise any device knownin the art that can determine, evaluate, or measure the degree ofelectrical activity of muscle cells, including invasive and non-invasiveelectrodes. Non-invasive electrodes, or surface electrodes, assessmuscle functioning by recording evoked muscle responses from the skinsurface (above the muscle). Surface electrodes are secured on the skinand are able to provide an assessment of the evoked muscle responsesbelow. While a surface electrode is placed over the muscle on the skin,with invasive electrodes, a needle electrode is inserted through theskin into the muscle to record the electrical activity of that muscle.Needle electrodes assess voluntary motor activity as can be done withsurface electrodes, as well as ‘insertional’ activity which occurs whenthe needle is inserted into the muscle.

In some embodiments, monitoring system 100 further comprises anautomated machine, including a disposable apparatus with both thestimulating probe and recording probe. Furthermore, in some embodiments,monitoring system 100 is configured to produce an output that isstandard and can plug into any given anesthesia machine to allow forcontinuous monitoring throughout the case.

In some embodiments, recording device 120 may be configured tocontinuously monitor the electrical activity in a muscle of a humanbeing in response to a low voltage electrical stimulus applied bystimulation electrode device 110. For example, recording device 120 canrecord spike discharges produced by the stimulated muscle, which is seenas a “spike focus.” The spike focus is normally a function of time andis describable in terms of its amplitude, frequency and phase, measuringelectrical currents generated in muscles during its contraction whichrepresent neuromuscular activities.

Thus, in one embodiment, recording device 120 may comprise surfaceelectrodes (as shown in first system 102) or needle electrodes (as shownin second system 104). In other words, recording device 120 can beapplied to the surface of the skin or can include a type of pin that isinserted into the skin. For example, with a needle EMG, a needleelectrode may be inserted directly into a nerve to record the electricalactivity associated with a particular muscle. It should be understoodthat the recording device is generally disposed on a patient's anatomyin such a location so as to correspond to or allow recording of theelectrical activity of the muscle that is being stimulated by thestimulation device.

In other embodiments, monitoring system 100 can include an optionalconnecting device that allows stimulation electrode device 110 andrecording device 120 to be readily manipulated in concert, and becorrectly positioned on a patient. For example, as shown in FIG. 1,monitoring system 100 includes a strip 130. In some embodiments, strip130 may include a disposable material, where monitoring system 100 is aone-time use system, facilitating the hygienic utilization of monitoringsystem 100. However, in other embodiments, strip 130 is a reusableportion of material that can be easily cleaned and used during multipleprocedures. Furthermore, in some embodiments, strip 130 may include anadhesive to allow for the easy application of monitoring system 100. Inone embodiment, strip 130 can be an elongated material designed forready and comfortable application and/or removal from a patient'sanatomy.

Furthermore, in some embodiments, monitoring system 100 can comprise acomputer processing unit (“processing unit”) 140, which containssuitable processing and memory components to carry out the sensing andrecording functions of the system. Though in some embodiments processingunit 140 can be part of or integrated into recording device 120, inother embodiments processing unit 140 may comprise an independentcomponent of monitoring system 100. In different embodiments, processingunit 140 can be configured with an analysis board, which can connect orlink to a paralysis agent delivery device (“paralysis agent device”) oran anesthesia delivery machine, and/or may provide a means ofcommunicating information between different devices. Thus, in someembodiments, monitoring system 100 can be configured with an outputmeans that facilitates an easy connection or plug-in to standardanesthesia delivery machines (see FIGS. 9 and 10).

In order to better understand the disclosed embodiments, the processthrough which monitoring system 100 is operated and utilized isgenerally represented in the flow diagrams of FIGS. 2-4. FIG. 2represents an overview of an embodiment of a method of using theparalysis monitoring system during the pre-operation, operation, andpost-operation stages. Referring to FIG. 2, a first step 202 may involveattaching paralysis monitoring system to the patient. In other words,the stimulation device and the recording device can be positioneddirectly on or into the skin of the patient. This can include placementof a strip that is attached to both the stimulation probe and therecording electrode. In some embodiments, the stimulation probe ispositioned proximally to the nerve that is being stimulated, and therecording electrode is positioned distally at the muscle. Depending onthe procedure, the appropriate anatomy or position of the monitoringdevice can vary, though typically placement would be over the ulnarnerve in the forearm or over the tibial nerve in the leg andalternatively as well could be used on the facial nerve. Those are thethree most accessible access points. But is contemplated that any otherplace where a major nerve could be stimulated and a response obtainedwould be a possibility from median to femoral to sciatic to almost anynerve. In some embodiments, there may be a prior, concurrent, or laterstep of inducing anesthesia or a type of sedation in the patient.

A second step 204 can comprise establishing an initial calibrationbaseline. Further detail regarding second step 204 will be described inconjunction with the description of FIG. 3 below.

The initialization of the monitoring system can also occur during thisstep, as well as general preparation for continuous monitoring. A thirdstep 206 comprises rechecking the calibration baseline if the patient isintubated. In a fourth step 208, a paralytic agent is administered tothe patient. In a fifth step 210, the paralysis monitoring systemcontinuously monitors the patient's muscle responses to determine theonset of paralysis following the administration of a paralysis agent.Thus, after the system determines there is sufficient paralysis to beginthe operation or surgical procedure, the system can be configured tocontinuously monitor the paralysis of the patient during the surgicalprocedure. In some embodiments, the stimulation device repeatedlyprovides stimulations to the patient at the pre-programmed low intensityon an automated cycling schedule. In other embodiments, the schedulecould be run at different frequencies. For example, in one embodimentthe stimulation device can run between every 1-3 seconds up to every 1-4minutes, providing feedback and a continuous monitoring of the patienton a display screen.

Typically, upon administration of a paralysis agent, the spike dischargesignal (produced by electrical stimulation of the target nerve(s) andbeing recorded by the monitoring system) will diminish and can beentirely lost. In one embodiment, such a signal loss corresponds to aconfirmation that paralysis of the patient has occurred. In other words,as neuromuscular receptors and junctions become blocked, when the nerveis stimulated, the patient's muscle response decreases or is lost. Whilethe paralytic agent is in the patient's system, the stimulus shocks donot produce a response in the muscle. Throughout the procedure,intermittent stimulus shocks may be administered, providing for anongoing, continuous monitoring of the patient.

As the administered paralysis agent(s) wears off, a percentage return ofthe response signal will occur. Thus, a response to the single pulsestimuli begins to return, indicating that the functional phase of theparalytic agent is progressively declining. In a sixth step 212, theparalysis monitoring system continuously monitors the recovery of thepatient and the return of muscle responses as shown by spike discharges.In some embodiments, the percentage return that is associated with therecovery of the patient's muscle activity can be approximately 50%. Inother embodiments, the range may be between 20% and 80%. Thus, thestimulus device continues to administer intermittent single shock pulsesto the patient, and the recording device continuously records theelectrical activity of the muscles throughout the operation, and afterthe operation. The system can be configured to automatically transmitpulses to the patient and notify a user if there is any return of theresponse signal. In an optional seventh step 214, the system cancontinuously monitor the patient in the post-anesthesia stage, ensuringthat there is no recurrence of paralysis or a reactivation of theeffects of the paralytic agent.

As a patient begins to regain the ability to move (as the paralysisreverses), there is an increasing graded percentage of return of thesignal being measured by the monitoring system. Over time, the recordedresponses to the stimulation impulses increase in intensity, untileventually returning to the baseline level, providing verification thatparalysis has fully worn off. After this occurs, the paralysismonitoring system can be removed from the patient, as represented in aneighth step 216. Furthermore, it should be understood that after theprocedure (i.e., during the post-operation stage) the paralysismonitoring device can continue to stimulate nerve(s) in a patient andrecord any corresponding muscle activity.

Thus, the monitoring system can be used to ensure the patient maintainsa certain paralysis level as needed by a surgeon to complete theprocedure and can also be used to ascertain the amount of paralysisresidual at the end of the procedure. Thus, the monitoring system canhelp determine whether there has been full metabolism of the paralyticagent and whether the patient is safe to extubate.

In some embodiments, the monitoring system can be left in position withan alarm in the postoperative recovery room, providing continuousmonitoring of the patient's paralysis. For example, if a reversal agentis used and re-paralysis occurs, an alarm can be triggered if there is aloss of the signal or partial loss of the signal, indicating that theparalysis is returning inadvertently.

As noted above, in some embodiments, the post-operative process can besimilar to the operation of the system during the procedure oroperation. For example, once a patient has entered the post-operativestage, the paralysis monitoring system may remain attached or connectedto the patient. The system may continue to transmit low voltageelectrical impulses to the patient as well as continuously monitor themuscle activity of the patient. Often a patient remains in partialparalysis following the completion of the procedure. As noted above, insome embodiments, the monitoring system may also be utilized as apostoperative paralysis monitoring system. In the cases in which thepatient has awakened from anesthesia yet remains paralyzed, themonitoring system may continue to show profound paralysis while othersigns of waking up would be registered, such as increased heart rate,increased blood pressure, and/or some jerky or twitching motions. Thus,the monitoring system can indicate that the patient is awakening but istoo paralyzed to move functionally. In one embodiment, the paralysismonitoring system can be configured with an alarm or other type of alertthat the spike discharge recordings have begun to indicate a return ofresponse signals or muscle activity, or an alarm that alerts thehealthcare professional that the patient has begun to awaken yet remainsin paralysis.

The monitoring system can be utilized regardless of whether a reversalagent is used.

A reversal agent or drug is typically a competitive antagonist thatcompetes for a binding site. Thus, reversal agents are generallyadministered to block a paralyzing drug molecule from attaching to acell surface where it was exerting its effect. The reversal agents canact to speed the muscle recovery process, but there are significant sideeffects associated with the use of reversal agents, and reversal agentsmay not be reliable, and are certainly not as reliable as the passage oftime in decreasing the effects of paralytic agents. As noted above,there are many risks associated with the patient's recovery fromanesthesia and paralysis, and a system that can continuously monitor thereturn of muscle activity during recovery can help prevent unnecessarytrauma to a patient.

FIG. 3 illustrates in more detail the exemplary initialization andpreparation for continuous monitoring step 204. In FIG. 3, in order toinitialize and begin continuous monitoring of a patient, a low voltagesignal may be transmitted from the stimulation device or electrode tothe nerve in a first step 302. The low voltage signal can cause a changein muscle activity in the patient, which is received as an electricalsignal by the recording device in a second step 304. In someembodiments, this can involve the monitoring system being turned on witha standard series of single impulses, and baseline stimulation responsesbeing recorded, as shown in a third step 306. Thus, in some embodiments,the monitoring system applies an intermittent pulse that is repeatedperiodically, e.g., every several seconds or other time period. Themonitoring system measures and records the response to the single pulsestimulation to determine the effect of the paralytic agent.

The baseline stimulation runs can be automated or manually operated indifferent embodiments. For example, an automated mode could transmitstimulations through an incremental pre-programmed ‘auto-cycle’ ofvoltage levels (for example, from 0.1 my to 2.0 my, etc.). In oneembodiment, the cycle would increase the intensity of stimulation untilthe system registered a predetermined response at the muscular interfacethat indicated a good connection of the device for that given patientand system placement.

The continuously recorded spike discharge activity can be stored andcompared with previously recorded spike discharge activity in a fourthstep 308. In a fifth step 310, the paralysis monitoring system evaluateswhether there have been a sufficient number of similar recorded signalsto establish a baseline recording for that patient. If the answer isyes, the baseline is established in a sixth step 312. If there are notyet a sufficient number of signals recorded by the system, the systemwill repeat the application of low voltage signals to record evokedmuscle responses until a baseline recording can be established.

In different embodiments, during a baseline recording, a direct spikefocus is obtained that corresponds to a baseline mode as well as adirect up and direct down impulse that is the result of the direct shockstimulus (provided by the stimulation device). The millivolt stimulus(e.g., in the range 0.5-1.5 millivolts, or up to as high as 3 to 4millivolts, in some cases) is administered to the patient and themonitoring system analyzes the readings until a spike of certain heightover background noise that it is repeatable and obtainable is recorded.In some embodiments, the spike discharge is at least 200% above thebackground noise level spike. In one embodiment, the spike discharge isat least 500% above the background noise level spike, such that thebaseline spike discharge is easily obtainable. In different embodiments,the baseline recording allows the monitoring system to account forpatient variables, such as skin temperature, skin depth, the fattycontent of skin, and/or the relative distances the stimulation probe andrecording probe are located from the nerve, and other such variables.Thus, slight differences in electrodes, individual characteristics suchas subcutaneous fat, skin thickness, or oil and/or hair on the skinsurface, and other factors that vary the levels of electrode impedancecan significantly modify the values of the electrical discharge. Byappropriate selection of spike discharge levels over noise, themonitoring system automatically accounts for these type of variables.

In some embodiments, baseline recordings could also be used to filterout fasciculations, which are brief, spontaneous contractions that canaffect muscle fibers, often causing a flicker of movement under theskin. In one embodiment, such background noise could be filtered outwith a timing mechanism that would time the stimulation pulse to thesignal and filter out background noise fasciculations. Thus, a baselinerecording by the monitoring system provides an indication of the of theindividual's muscle activity that can be used to calibrate the signal.In other words, the baseline recording can serve as a basis ofcomparison for subsequent data collection. Because these types offactors can also affect the amount of current that is required toprovide accurate stimulation, the baseline recording offers anadvantageous reference point throughout the monitoring process.

Further detail regarding exemplary third step 210 through fifth step 210is provided in the flow diagram of FIG. 4. Referring to FIG. 4,following administration of a paralysis agent in a first step 402, itbecomes of paramount importance to ascertain whether the patient hasbecome paralyzed. As noted above, the paralysis monitoring system canintermittently send a low voltage signal to the patient's nerves, andthe recording device receives and records any spike discharge signal inorder to monitor the condition of the patient. Thus, the system cancontinuously monitor the patient to verify a loss of signal and confirmthat paralysis has been established in a second step 404.

The received response signal (RS) may be compared to the baseline spikedischarge recording using conventional circuitry such as comparators,memories and the like. If the received signal is less than the baselinespike discharge recording by a specified amount or delta, the systemdetermines that the patient has been successfully paralyzed, and thesurgical procedure may begin. If the difference between the receivedsignal and the baseline spike discharge recording is insufficient, thesystem continues to monitor the muscle activity. In a third step 406,the system determines whether a signal is returning. If there is nosignal, the system continues to monitor the patient and verify thatparalysis is established. If a signal returns, indicating the paralysisis wearing off as in step 407, the system can continue to monitor thepatient until the paralysis has been fully reversed and the condition ofthe patient is deemed safe for extubation, as shown in a fourth step408. In some embodiments, monitoring can continue during thepost-operative period as well. However, in other embodiments, thepatient may instead be optionally re-dosed to return the patient to astate of paralysis.

If additional paralysis agent is administered, it should be understoodthat there would be a repeat loss of the signal when the patient becomesfully re-paralyzed. However, in many cases, total paralysis may not berequired by the procedure. In some instances, for example, a healthcareprofessional may determine that an 80% reduction in the signal intensityor height of the spike discharge is sufficient. In other words, thepercentage reduction need not be 100% in order for a patient to bedeemed clinically paralyzed and able to continue the surgical therapy.As the additional paralytic agent wears off entirely, there is a returnof the signal to complete baseline, indicating a 100% functional returnto the preoperative level, assuming no other changes have occurred inthe patient which might affect the response signals. For example, if thepatient is very cold there can be effects upon the ability to stimulatethe nerve.

Thus, during post-surgery recording, the spike discharges would bedisplayed as 100% of the baseline recording level, corresponding to thecondition in which the patient is awake and able to move normally. Ifthe patient is still weak but able to move somewhat, it is anticipatedthat the spike discharge will be a percentage of normal (for example,between 40% to 80% of the baseline recording level). However, theadditional or repeat dosing step depicted in FIG. 4 should be understoodto be optional, and continuous monitoring can occur without anyadditional paralytic agent.

In order to provide greater clarity, FIGS. 5-8 illustrate embodiments ofthe paralysis monitoring system during a typical procedure withexemplary spike discharge readings. As shown in FIG. 5, the monitoringsystem 100 has been placed on or attached to a patient 500. In thisexample, monitoring system 100 has been positioned along an arm 520 ofpatient 500. Stimulation electrode device 110 and recording device 120are arranged along strip 130 and are disposed on a nerve such as theulnar nerve in the forearm. However, in other embodiments, monitoringsystem 100 can be disposed along any other portion of a patient'sanatomy that enable access to stimulate and response from a major nerveincluding median to femoral to sciatic to almost any nerve. Furthermore,it can be seen that monitoring system components (such as stimulationelectrode device 110 and/or recording device 120) can be connected to asignal processor, which can also be connected to a monitor or display510.

As monitoring system 100 is activated, a baseline recording of themuscle responses of patient 500 is taken, as described earlier withrespect to FIG. 4. In FIG. 5 it can be seen that a display 510 includesonly the patient's baseline signal (which was established and recordedearlier). After a paralysis agent is administered, the spike dischargerecording changes, as shown in the example of FIG. 6, where a paralysisspike discharge recording 600 on display 510 illustrates how the signalis effectively ‘lost’ as muscle responses become minimal as paralysissets in. The approximate signal loss relative to the baseline signal isdisplayed as a percentage, such as 30% shown in FIG. 6, although inother embodiments, different graphical icons or images can be presented,such as a pie chart or other visual indicators. The amount of signalloss can vary throughout the procedure.

Over time, the paralysis agent can wear off, and there is a progressivereturn of muscle activity, represented in the embodiment of FIG. 7 as arecovering spike discharge recording 700. FIG. 7 shows that the loss ofsignal is increased from 30% in FIG. 6 to 50%. Eventually the spikedischarge signal grows in strength until the muscle activity returns tolevels associated with the baseline spike discharge recording. In somecases, as noted above, muscle activity can begin to return during aprocedure. When a paralytic agent wears off during surgery, themonitoring system is able to determine the level of reversibility in thepatient.

Referring to FIG. 7, patient 500 is shown as a progressive return ofmotor activity is occurring. Monitoring system 100 can assess andevaluate the return of motor activity by the increasing percentage ofspike foci, to help determine whether additional micro-doses ofparalytic agent are needed. In some embodiments, this determination canbe based in part on factors inputted by a user into the system such asthe length of the case and/or the patient's sensitivities or metabolism.

In different embodiments, the monitoring system can comprisecommercially available components that are used routinely inneurostimulation and/or EMG recording. In addition, as noted above, themonitoring system can include a computer or other processing unit thatcan be configured to process the signal, to run the autocalibrationcycle, and/or to print out or display the percentage of baselineactivity available and send that information to the anesthesia machine.

FIG. 8 shows examples of a surface electrode for stimulation of a nerve.An example of a commercially available stimulus generator 802 that maybe used in embodiments is the Stimuplex HNS-12 model made by B. Braunshown in FIG. 9, which may be operated to stimulate nerves between 0.1to 4 mV in accordance with the principles of the invention. The surfaceand recording electrodes may be commercially available electrodes, suchthose packaged with Stimuplex HNS-12 stimulus generator. Furthermore, insome embodiments, a commercially available monopolar point impulsegenerator 804, such as the Direct Nerve Stimulator Probe available fromFriendship Medical Electronics shown in FIG. 10, can be utilized tostimulate the nerve. In other embodiments, a bipolar stimulating probemay be used, such as the Bipolar Nerve Stimulator Probe, FriendshipMedical Electronics. The monitoring system can also include a computerprocessor and recording monitor unit (such as the commercially availableNicolet Viking Viasas recorder monitor), which can be used to record,print and analyze EMG waveforms. In some embodiments, an additionalsurface electrode could be applied in FIG. 8 for EMG recording.

In different embodiments, the stimulus device could provide either astandard input or a variable self-calibrating device. In addition, insome embodiments, the monitoring system could include stimulus probesplaced in different locations. Furthermore, the disclosed embodimentscould include magnetic stimulation to the brain or more proximal nerves,could involve alternative recording techniques for EMG through the skinwith the standard pin recordings, and/or could involve so differentanalysis endpoints in the processing to state the percentage ofparalysis that are present.

Some of the concepts described herein have been tested by the inventor.The test involved the use of standard, commercially available equipmentfor nerve stimulation. During testing, stimulus probes were placed onthe skin of the inventor using the Stimuplex HNS-12 model generatorshown in FIG. 9 and a nerve in the arm was stimulated between 0.1 mV to0.2 mV. A strong response in the muscle interface was produced andrecorded. During the testing, there was no sensation from the stimulusprobe voltage. The stimulus voltage was increased progressively to thelevel typically used in the conventional train-of-four technique, whichcaused a physical twitch in the arm, whereby the stimulus became painfuland left a persisting tingling feeling in the arm ranging from a fewminutes to half an hour or more. In addition, during this initialtesting, the monitoring system prototype was also tested for instancerecording as well as the surrounding muscles both proximal and lateralto the plane of intervention to make sure there was no noise or a spreadin the impulse, to ensure that the recording accurately representedneural-to-motor interface of the particular nerve and also to look atranges and repeatability.

Systems constructed according to the inventive principles discussedherein provide a considerable improvement over conventional techniquesby allowing a continuous monitoring including providing a printout tothe anesthesiologist. The monitoring system of the invention determines(a) the depth of paralysis present, (b) the level of reversibility ofthe patient, and/or (c) a safety margin for extubation. Furthermore, themonitoring system provides for continuous monitoring in thepostoperative period, which helps prevent postoperative re-paralysisand/or death from respiratory arrest. Thus, monitoring systemsconstructed according to the principles of the invention provide adramatic decrease in the risks associated with paralysis duringprocedures requiring anesthesia and/or simplify the process of paralysismonitoring in a standardizable fashion. In addition, monitoring systemsof the invention overcome disadvantages of conventional paralysismonitoring techniques, which rely upon crude visual observation ofmuscle responses, and do not account for the variability of patientphysical characteristics such as skin thickness, temperature of thepatient's extremities, etc., with a reliable neuromuscular recordingpossible with the inventive concepts. As noted earlier, it is alsoessential to ascertain that the effects of neuromuscular blocking drugshave worn off or are reversed before the patient regains consciousness.For example, even after paralytic agents wear off, residual paralysisremains an issue, in spite of the availability of shorter-actingneuromuscular blocking drugs. Thus, monitoring system embodiments of theinvention dramatically increase the safety of the patient and helpprevent historically multiple postoperative deaths that are recorded peryear, as well as postoperative respiratory arrests.

Furthermore, it should be understood that in some embodiments the autocalibration system as disclosed herein obtains a baseline stimulus thattakes into account (a) the temperature of the skin; (b) the distance theprobe may be from the nerve; and (c) the contact of the recordingelectrode (i.e., whether surface or pin will determine adequacy of therecorded stimulus). In an exemplary embodiment, the baseline recordingwould be at least ten times the background noise. Furthermore, thebaseline calibration would confirm the proper placement of the electrodepatch, ensuring that the electrode will generate a stimulus/response inan acceptable range of stimulation. If an adequate response is notobtained the patch would need to be repositioned or the contactschecked. However, in other embodiments, the range can vary. Once thebaseline is established and the electrode placement is correct, thatsignal would become the baseline signal to which continuous monitoringsignal would be compared. In other words, the loss of that baselineindicates a paralyzed state. As a patient begins to recover, theparalysis wears off in a graded or a percentage fashion. Once baselineis reestablished, the patient can be safely extubated. Thus, the end ofanesthesia would be pending a complete return of the signal to baseline.In addition, postoperative monitoring is important because often areversal agent is used which is known to work for a short duration, butthere may be residual paralytic agent that outlasted the procedure, andthe patient may slip back into a partial paralyzed state.

In some embodiments, the use of the monitoring system comprises asequence of steps. A first step comprises obtaining a baseline aftersedation, prior to the administration of any paralytic agents. A secondstep comprises switching on continuous monitoring after the autocalibration is complete. A third step involves a continuous monitor andobservation of the loss of signal during onset of a paralytic agent. Afourth step occurs when the continuous monitor records the beginning ofa percentage of return of the spike discharge, indicating the paralysisagent is wearing off. In a fifth step, an anesthesiologist can determinewhether to administer more agent, for example, in the case where thesurgeon requires additional time to complete the procedure. A sixth stepinvolves confirmation of a return of the full baseline signal prior toending in a static procedure, and the extubation of the patient. Theseventh step comprises continuous monitoring in the recovery room untilthe patient is fully awake, in order to avoid a relapse to paralysis.

In the presence of a neuromuscular blockade an operator of a paralysismonitoring system would not expect to see a strong response to astimulating voltage. Therefore, to ensure the monitoring system isoperating properly, some embodiments may include provisions for takingan independent measurement or reading of electrical signals from alocation away from a target muscle group. For example, measuringelectrical signals from nearby soft tissue (e.g., nearby to, but not on,the target muscle group) can provide an independent reading from therecording electrodes located over the target muscle group. Theindependent measurement may record an electric signal that is distinctfrom the signal detected at the muscles during stimulation. The presenceof an electrical signal that appears to correspond with the timing (orother characteristic features) of any electrical signals generated at astimulating device may help confirm that the stimulating device is notmalfunctioning even when a low response is seen at the muscle group(because of a neuromuscular blockade).

FIG. 11 is a schematic view of an embodiment of a patient's arm 900. Amonitoring system 901 includes a stimulation electrode device 910 (orsimply “stimulation device”) and primary recording device 912.Stimulation device 910 and primary recording device 912 are arrangedalong a first strip 902 and are disposed on a nerve such as the ulnarnerve in the forearm. Primary recording device 912 may be disposed overa target muscle region 915, which corresponds to the muscles that may bedirectly affected by the stimulation of the nerve targeted bystimulation device 910.

Monitoring system 901 includes a secondary recording device 914. In someembodiments, secondary recording device 914 is disposed on a secondstrip 904 that may be attached to first strip 902. Secondary recordingdevice 914 may be disposed over a soft tissue region 916 that isdisplaced from target muscle region 915.

Although each of stimulation device 910, primary recording device 912and secondary recording device 914 are shown schematically as electrodedevices, the exemplary embodiment could utilize any kind of stimulationdevice and/or recording device. In some cases, needles or othersubcutaneous probes could be used. Moreover, any kind of stimulationand/or recording device disclosed previously with respect to theembodiment of FIGS. 1-10 could also be used.

In different embodiments, the locations of each recording devicerelative to a stimulation device could vary. In some embodiments, eachrecording device could be disposed on a common axis with a stimulationdevice. In other embodiments, each recording device may be located on adifferent axis with respect to a stimulation device. In the embodimentshown in FIG. 11, first strip 902 may be characterized by a lengthwiseaxis 930 that runs approximately parallel with the length of arm 900. Incontrast, second strip 904 may have a second lengthwise axis 932 that isoriented at an angle to lengthwise axis 930. In some cases, axis 930 andaxis 932 may be disposed at an angle 940 with respect to one another. Insome cases, angle 940 could range between approximately 0 and 90degrees. In some embodiments, angle 940 may range between approximately30 and 60 degrees. In one embodiment angle 940 have a value ofapproximately 45 degrees.

Each recording device can also be located a different overall distancefrom a stimulation device. In some embodiments, a primary recordingdevice (i.e., a device disposed over a target muscle region) may bedisposed closer than a secondary recording device (i.e., a devicedisposed over another soft tissue region that is different from thetarget muscle region) to a stimulation device. In other embodiments, aprimary recording device could be disposed further from a stimulationdevice than a secondary recording device. In still other embodiments, aprimary recording device and a secondary recording device could beapproximately equidistant from a stimulation device. In the exemplaryembodiment shown in FIG. 11, primary recording device 912 is disposedfurther from stimulation device 910 than secondary recording device 914.Specifically, primary recording device 912 may be disposed a firstrecording distance 950 from stimulation device 910 and secondaryrecording device 914 may be disposed a second recording distance 952from stimulation device 910. In some embodiments, second recordingdistance 952 may be approximately in a range between 30% and 70% offirst recording distance 950.

In some cases, the exact location (and relative distance to astimulation device) of each recording device can be selected accordingto factors including stimulation voltage levels (and/or currents),patient characteristics (such as body fat, size of target muscle group,etc.), sensitivity of the recording devices as well as possibly otherparameters. It may be appreciated that locating a secondary recordingdevice away from the target muscle group may allow for recording ofelectrical signals that may be independent of the muscle response (whichmay be affected by neuromuscular blockades). Such independently recordedsignals can be used to determine that a monitoring system is operatingproperly (e.g., that a stimulating device is functioning correctly andsending out electrical pulses of desired voltages and intervals).

FIG. 11 includes two schematic views of signals that have beenindependently recorded by primary recording device 912 and secondaryrecording device 914. These include a first electrical signal 960detected at primary recording device 912 and a second electrical signal962 detected at secondary recording device 914. It may be appreciatedthat the exemplary signals are shown for schematic purposes and they mayor may not be visible on a monitoring screen during a procedure in someembodiments. As in the embodiments described above and shown in FIG. 5,the components of monitoring system 901 (such as stimulation device 910,primary recording device 912 and secondary recording device 914 mayconnected to a signal processor (not shown in FIG. 11), which can alsobe connected to a monitor or display.

As seen in FIG. 11, first electrical signal 960 and second electricalsignal 962 may have different waveforms or waveform characteristics. Forexample, first electrical signal 960 includes regions of baseline noisewith a large peak 970 corresponding to a muscle response. Secondelectrical signal 962 includes a moderately sized peak 974 followedimmediately by a large dip 976. It may be appreciated that firstelectrical signal 960 and second electrical signal 962 have distinctwaveforms that may not only be distinguished by quantitative analysisbut may also be qualitatively distinct.

It may be appreciated that in some cases, electrical signals detected atsecondary recording device 914 (e.g., second electrical signal 962) maybe associated with electrical signals generated by stimulation device910 (i.e., low voltage electrical impulses) that have spread tosurrounding tissue but have not evoked a muscle response. That is, aslow voltage impulses are generated at stimulation device 910, some ofthe electrical energy that is generated may stimulate the underlyingnerve (and thus evoke a muscle response via the nerve), and some of theelectrical energy may be dissipated into surrounding tissue withoutstimulating the nerve. It is this latter part of the electrical signalthat may, in some cases, be detected by second recording device 914.Alternatively, in some cases second recording device 914 may detectelectrical energy that has been generated at a nerve and/or at a muscle.It should be understood that while the underlying source (or sources) ofthe electrical signal(s) measured at the second recording device 914could vary in different situations, the monitoring system may be usefulwhenever the signals detected at second recording device 914 aresubstantially different from the signals detected at first recordingdevice 912 (in a quantitative and/or qualitative sense).

Moreover, it may be appreciated that the features (e.g., peak 974 anddip 976) recorded by secondary recording device 914 are sufficientlydistinct from any background or baseline noise so as to be immediatelyidentifiable as a response to a pulse from stimulation device 910. Intrial uses of the exemplary device such waveforms have been observed tohave a distinct characteristic from muscle response waveforms. It may beinferred therefore that these signals are an artifact of the system thatis distinct from the electrical signals generated at the muscle duringcontraction. For reference, these distinctive waveforms measured atlocation away from a target muscle group may be referred to as“stimulation artifacts” as they allow a doctor or technician to inferthe presence of a stimulating signal but are unrelated, or indirectlyrelated, to direct muscle response signals.

Using the above embodiment of a monitoring system, it is possible for adoctor or technician to confirm that a monitoring system is operating asexpected. Specifically, a doctor or technician may observe a responsesignal near the stimulation source even when a neuromuscular blockadeprevents a primary recording device from detecting evidence ofelectrical signals above the baseline signal.

FIG. 12 is a schematic view of a process of using a secondary recordingdevice to confirm that a monitoring system is operating properly. It maybe appreciated that some or all of the following steps could be combinedwith any of the processes described above and shown, for example, inFIGS. 2-4. In some embodiments, the following steps for checking that amonitoring system is functioning properly could be done towards thebeginning of an overall paralysis monitoring process. In otherembodiments, the following steps could be done throughout a monitoringprocess either at regular intervals or continuously. Moreover, it may beunderstood that the following process could be performed manually by adoctor or technician (i.e., by pushing buttons and visibly monitoringresponses), automatically by a machine, and/or some combination ofmanual and automated steps.

In a first step 1000, a stimulation device (e.g., stimulation device910) may be instructed to generate one or more low voltage impulses tostimulate an underlying nerve. As described above, the low voltageimpulse may be at a level that is insufficient to cause visible muscletwitch or contraction. Next, in a step 1002, the operating condition ofthe system may be checked by confirming that a signal has been receivedat a secondary recording device (e.g., recording device 914) that islocated away from the target muscle region. Moreover, during this step,the signal may be analyzed to determine if the signal is consistent witha low voltage impulse being generated by the stimulation device. Aspreviously discussed, in some cases this can be done manually byvisually inspecting that the second recording device is measuringsignals with qualitatively distinct waveforms known to be associatedwith stimulation impulses.

If, during step 1002, the expected signal is detected at the secondrecording device, it may be determined that the system is functioningproperly in step 1004. At this point the process may proceed toanalyzing the signals detected at the primary recording device todetermine a paralysis level during step 1005. This step may include anyof the processes described above and shown in FIGS. 2-4 for paralysismonitoring. Alternatively, if during step 1002, the second recordingdevice does not record any signals that would indicate the presence oflow voltage impulses at the stimulation device, then it may bedetermined that the system is not functioning properly in step 1006. Atthis point, a troubleshooting process may be used to determine apossible cause for the malfunction in step 1008.

In some embodiments, a paralysis monitoring system may use informationfrom a second recording device to interpret signals received at a firstrecording device. For example, the information from signals recorded atthe second recording device could be used to select, or filter, orotherwise modify, the signals received at the first recording device.

FIG. 13 is a schematic view of a set of electrical signals. Here a firstsignal 1102 corresponds to an exemplary signal that may be received at afirst recording device located over a target muscle region. First signal1102 signal includes clear response peaks that indicate a response inthe muscles to nerve stimulation. A second signal 1104 corresponds to anexemplary signal that may be received at a second recording devicelocated away from the target muscle region. Second signal 1104 includesdistinctive waveform regions 1105 that are indicative of low voltageimpulses being generated from a nearby source (i.e., a stimulationdevice). A third signal 1106 corresponds to a filtered signal that isdetermined using information from first signal 1102 and second signal1104. As used herein, the term “filtered” simply refers to the usinginformation from one signal to modify another signal. In some cases,filtering could refer to direct subtraction of one signal from another.In other cases, filtering could refer to first transforming the secondsignal (e.g., translating it by an offset and/or inverting it) and thensubtracting it from the first signal. In still other cases, filteringcould refer to a more general process whereby information from thesecond signal is used to modify the first signal.

In some embodiments, filtering the first signal using information aboutthe second signal may act to clean up the first signal. That is, thefiltering process could help reduce noise or other information from thesignal that is not directly related to signals generated during anevoked muscle response to the stimulating impulses. In some embodiments,the second signal could be used to decide if a particular waveform inthe first signal may in fact be a muscle response signal or just noise.That is, the second signal may be used to select for true responsesignals.

For clarity, the detailed descriptions herein describe certain exemplaryembodiments, but the disclosure in this application may be applied toany types of stimulation devices and/or recording devices suitable forproviding low voltage stimulation to nerves and recording the muscleresponse thereto. While various embodiments have been described, thedescription is intended to be exemplary, rather than limiting and itwill be apparent to those of ordinary skill in the art that many moreembodiments and implementations are possible that are within the scopeof the embodiments. Although many possible combinations of features areshown in the accompanying figures and discussed in this detaileddescription, many other combinations of the disclosed features arepossible. Any feature of any embodiment may be used in combination withor substituted for any other feature or element in any other embodimentunless specifically restricted. Therefore, it will be understood thatany of the features shown and/or discussed in the present disclosure maybe implemented together in any suitable combination. Accordingly, theembodiments are not to be restricted except in light of the attachedclaims and their equivalents. Also, various modifications and changesmay be made within the scope of the appended claims.

What is claimed is:
 1. A paralysis monitoring system comprising: a nervestimulation device configured to deliver a series of low voltageelectrical impulses to a nerve to produce only sub-visible muscleresponses, wherein the low voltage electrical impulses are 4 millivoltsor less; a recording device configured to record electrical activityassociated with an evoked muscle response caused by the series of lowvoltage electrical impulses; wherein the nerve stimulation device isconfigured to transmit the low voltage electrical impulses to a patientbased on a body mass index of the patient; wherein the nerve stimulationdevice is configured to transmit the low voltage electrical impulses inthe range of about 0.5 millivolts to 1.5 millivolts to patients having abody mass index in a first range; and wherein the nerve stimulationdevice is configured to transmit the low voltage electrical impulses inthe range of about 1.5 millivolts to 4 millivolts to patients having abody mass index in a second range that is higher than the first range.2. The paralysis monitoring system according to claim 1, wherein thenerve stimulation device and the recording device are disposed on astrip.
 3. The paralysis monitoring system according to claim 1, whereinthe recording device comprises an electrode or a needle.
 4. Theparalysis monitoring system according to claim 1, wherein the nervestimulation device comprises a transcutaneous electrode probe configuredto transmit milliamp current.
 5. The paralysis monitoring systemaccording to claim 1, wherein the nerve stimulation device is configuredto provide the low voltage electrical impulses on an automatic cyclingschedule.
 6. The paralysis monitoring system according to claim 5,wherein the automatic cycling schedule transmits the low voltageelectrical impulses on an incremental basis from 0.1 millivolts up to 2millivolts.
 7. A method of administering a paralysis drug to a patient,the method comprising: attaching a nerve stimulation device to apatient's anatomy; attaching a recording device to the patient'sanatomy; administering a first dose of a paralysis agent to the patient;transmitting low voltage electrical impulses from the nerve stimulationdevice to the patient, wherein the low voltage electrical impulses are 4millivolts or less; receiving a response signal corresponding to muscleactivity of the patient in the recording device; using informationrelated to the response signal to determine an amount of the paralysisagent to administer as a second dose; and administering the second doseof the paralysis agent to the patient; wherein the nerve stimulationdevice is configured to transmit the low voltage electrical impulses tothe patient based on a body mass index of the patient; wherein the nervestimulation device is configured to transmit the low voltage electricalimpulses in the range of about 0.5 millivolts to 1.5 millivolts topatients having a body mass index in a first range; and wherein thenerve stimulation device is configured to transmit the low voltageelectrical impulses in the range of about 1.5 millivolts to 4 millivoltsto patients having a body mass index in a second range that is higherthan the first range.
 8. The method according to claim 7, wherein thelow voltage electrical impulses have magnitudes to produce onlysub-visible muscle responses.
 9. The method according to claim 7,wherein using information related to the response signal includescomparing the response signal to a baseline recording of the patient'smuscle activity.
 10. The method according to claim 9, wherein the seconddose of the paralysis agent is administered if the response signal issubstantially similar to the baseline recording.
 11. The methodaccording to claim 7, the method further comprising attaching a secondrecording device to the patient's anatomy, wherein the second recordingdevice is located away from the first recording device.
 12. The methodaccording to claim 11, wherein the method further comprising checkingthat electrical signals corresponding to the low voltage impulses arerecorded at the second recording device.
 13. The method according toclaim 11, the method further comprising using information from a secondresponse signal recorded at the second recording device to interpret theresponse signal received at the recording device.
 14. The paralysismonitoring system according to claim 6, wherein the low voltageelectrical impulses are increased until a predetermined muscle responseis received by the recording device.
 15. The paralysis monitoring systemaccording to claim 1, wherein the recording device is configured torecord a spike focus of the evoked muscle response.
 16. The paralysismonitoring system according to claim 1, further comprising an alarmconfigured to provide an alert upon detecting a return of responsesignals or muscle activity of a patient.
 17. The paralysis monitoringsystem according to claim 1, wherein the paralysis monitoring system isconfigured to apply an intermittent pulse that is repeated periodically;and wherein the paralysis monitoring system is further configured tomeasure and record a response to the intermittent pulse to determine aneffect of a paralytic agent.
 18. The paralysis monitoring systemaccording to claim 1, further comprising a signal processor incommunication with the recording device.
 19. The paralysis monitoringsystem according to claim 18, wherein the signal processor is connectedto a display.
 20. A paralysis monitoring system comprising: a nervestimulation device configured to deliver a series of low voltageelectrical impulses to a nerve of a patient to produce only sub-visiblemuscle responses, wherein the low voltage electrical impulses are 4millivolts or less; a recording device configured to record electricalactivity associated with an evoked muscle response of the patient causedby the series of low voltage electrical impulses; wherein the nervestimulation device is configured to provide the low voltage electricalimpulses on an automatic cycling schedule; wherein the recording deviceis configured to confirm paralysis of the patient when the low voltageelectrical impulses do not produce an evoked muscle response; whereinthe nerve stimulation device is configured to transmit the low voltageelectrical impulses to the patient based on a body mass index of thepatient; wherein the nerve stimulation device is configured to transmitthe low voltage electrical impulses in the range of about 0.5 millivoltsto 1.5 millivolts to patients having a body mass index in a first range;and wherein the nerve stimulation device is configured to transmit thelow voltage electrical impulses in the range of about 1.5 millivolts to4 millivolts to patients having a body mass index in a second range thatis higher than the first range.